Thiophosphonic acid esters



United States Patent Claims. in. zen-s The present invention relates toand has as its objects new and useful insecticidal thiophosphoric acidesters as well as methods for preparing the same. Generally thecompounds of the present invention may be represented by the followingformula in which R stands for any aliphatic or aromatic residue, R ispreferably a lower alkyl radical up to 4 carbon atoms, and R is aheterocyclic or acyl radical.

Compounds of this type, i.e. d-ithiophosphonic acid alkyl esters inwhich the alkyl group attached to the thiolosulfur contains asubstituted mercapto radical, partially are already known from theliterature. Their insecticidal properties are also known. According tothis invention a new class of especially substituted dithiophosphonicacid esters has been found .to exhibit outstanding insecticidal andpartially miticidal properties. More particularly the compounds of thisinvention are those of the above said formula R S (O) Rio in which R andR have the same significance as given above, and in which the acylradical R is the residue of a carbonic acid, thiocarbonic acid, carbamicacid, thiocarbamic acid, phosphoric acid, thiop-hosphoric acid,phosphonic acid, thiophonic acid, phosphonic acid, thiophosphonic acid,as well as amid derivatives of the latter compounds of the phosphorusseries. If R, is a heterocyclic group this radical preferably belong tothe thiazol, thio-diazol, imidazol, pyrazol, or triazol series or theirbenzene-annelled derivatives.

The inventive compounds may be prepared by methods known in principle,thus corresponding (thiono)phosphonic acid halides may be reacted withappropriate substituted mercaptans as it is to be seen from thefollowing equation:

Also in these formulae the symbols have again the same significance asgiven above.

A preferred method to prepare the inventive compounds consists inreacting the readily obtainable alkyl or aryl thiono-O-alkylesterthiolphosphonic acid alkali metal 3,248,412 Patented Apr. 26, 1966 saltswith chloro-bromo-rnethane. In this manner, compounds result having thegeneral formula i SCHzCl B 0 in which R and R have again thesignificance given above.

These a chloro-methyl-thiono-thiolphosphonic-O-alkyl esters may bereacted with suitable compounds containing sulfhydryl groups and, inthis way, the new phosphonic acid esters of this invention are obtainedwhich possess good insecticidal properties.

As compounds containing sulfhydryl groups there may be considered forexample: thiocarboxylic acids, dithiocarbamic acids, thiocyanic acid,Xanthogenates, thiol-acids of the phosphoric, phosphonic and phosphinicseries (or derivatives, e.g. amines thereof), and heterocyclicmercaptans as well as further similarly constructed or reactingcompounds.

For this purpose, especially the alkali metal salts of the aforesaidcompounds containing sulfhydryl groups are reacted with them-chloromethyl thiono-thiolphosphonic acid esters.

The new phosphonic acid esters are outstanding plant protective agentsor pesticidal agents which are used in a conventional manner, i.e.preferably in combination with suitable solid or liquid extending ordiluting agents optionally with the concurrent use of emulsifiers toimprove the d-ispersibility of the active compounds in water.

As an example for the special utility of the inventive compounds theesters of the following formulae have been tested against aphids andspider mites. Aqueous solutions of the aforementioned compounds havebeen prepared by admixing them with the same amount of an auxiliarysolvent (acetone). A commercial emulsifier (benzyl hydroxy diphenylpolyglycol ether) is added in an amount of 20% referred to activeingredient. This pre-mixture is diluted with water to the desiredconcentration.

The tests have been carried out as follows:

(a) against aphids (species Doralis fabae). Heavily infested bean plants(Vitz'a faba) have been sprayed drip wet with solutions in aconcentration as shown below and prepared as shown above. The effect hasbeen determined after 24 hours by counting the dead pests either on thesurface of the soil or still remaining on the plants. The followingresults have been obtained:

(b) against spider mites (species Tetranychus telarius Hanst.). Thetests have been performed on Phaseolus vulgaris. The plants have beensprayed drip wet with solutions as prepared above in a concentration asshown below. Evaluation has been carried out after 24 hours,

48 hours and 8 days. The spider mites were killed as shown in the tablebelow:

Aqueous concentration Compound The following examples are given for thepurpose of illustrating the process.

EXAMPLE 1 C3115 lS CzHsO 208 grams (1 mol) of ethyl-thiono-O-ethylesterthiolphosphonic acid potassium salt are dissolved in 400 ml. ofacetonitrile. 260 grams of chlorobromo-methane are added with stirringat 30-40 C. Stirring is continued for 3 hours at 40 C. and the reactionproduct is then taken up in 500 ml. of chloroform. The chloroformsolution is washed several times with water and subsequently dried withsodium sulfate. By fractionation 160 grams of ethylthiono-O-ethyl-S-a-chloro-rnethylphosphonic acid ester of B.P. 60C./0.01 mm. Hg are obtained. Yield: 73% of the theoretical.

0.001% solutions kill flies to 100%. Aphids are killed completely withsolutions of 0.01%. Ticks are killed completely with 0.025% solutions.0.001% solutions kill blowflies to 50%.

EXAMPLE 2 02115 S \ll 36 grams of thiobenzoic acid potassium salt aredissolved in 250 ml. of acetonitrile. 44 grams mol) of ethyl thiono Oethyl S a chloromethyl phosphonic acid ester are added with stirring at60 C. The mixture is maintained at 60 C. for 2 hours, and the reactionproduct is then diluted with 300 ml. of benzene. The benzene solution iswashed twice with 250 ml. of water. After drying of the benzene solutionit is fractionated. In this way, 50 grams of the new ester of B.P. 142C./0.01 mm. Hg are obtained. Yield: 89% of the theoretical.

Aphids are killed completely with 0.01% solutions. 0.001% solutions killspider mites to 100%.

By the same way but using instead of the thiobenzoic acid potassium saltthe corresponding equimolecular amount of thioacetic acid potassium saltand instead of the ethyl thiono O ethyl-s-u-chloromcthyl phosphonic acidester the exact equimolecular amount of the correspondingphenyl-thiono-O-ethyl-S-a-chloromethyl-phosphonic acid ester there isobtained the following compound:

EXAMPLE 3 C2H5O 48 grams of dimethyl-dithiocarbamic acid sodium salt aredissolved in 200 ml. of acetonitrile. 66 grams mol) ofethyl-thiono-O-ethyl-S-o-chloromethyl-phosphoic acid ester are addedwith stirring at C. Heating is continued to C. for an hour and thereaction product placed in 500 ml. of water. The separated oil is takenmol 303: N, 4.6%; S, 42.3%; P, 10.2%.

' solutions.

up in 300 ml. benzene and washed several times with water. The benzenesolution is dried. The solvent is subsequently distilled off in avacuum. In this way 82 grams of a viscous water-insoluble yellow oil areobtained. Yield of the theoretical. Calculated for Found: N, 4.3%; S,42.0%; P, 10.5%.

On rats per os the new compounds show a toxicity of 10 mg./kg. LD Spidermites are killed completely with 0.0001% solutions. 0.001% solutionskill aphids to Cockroaches are killed completely with 0.1%

By using instead of the sodium salt of dimethyl-dithiocarbamic acid thecorresponding equimolecular amount of the sodium salt ofdiethyl-thiocarbamic acid and instead of theethyl-thiono-O-ethyl-S-a-chlorornethylphosphonic acid ester thecorresponding equimolecular amount of avinyl-thiono-O-ethyl-S-a-chloromethyl-phosphonic acid ester there isobtained the following compound:

30 grams of potassium thiocyanate are dissolved in 100 ml. of 90%alcohol. 66 grams 7 mol) of ethyl-thiono- O-ethy1-S-ot-chloromethylphosphonic acid ester are added thereto at 3540 C. with stirring.Heating is continued to 85 C. for 5 hours and the reaction product thentaken up in 300 ml. of' benzene. The potassium chloride formed isfiltered off. The filtrate is washed several times with water andsubsequently dried with sodium sulfate. By fractionation, 50 grams ofthe new ester of B.P. C./ 0.01 mm. Hg are obtained.

On rats per os the ester shows a toxicity of 25 mg./kg. LD Files andspider mites are killed completely with 0.01% solutions. Larvae arekilled completely with 0.0001% solutions. 0.01% solutions kill bolwfliesto 50%.

EXAMPLE 5 CzHs S S 25 grams of potassium xanthogenate are dissolved in125 ml. of 95% alcohol. 32 grams (V mol) of ethylthiono-O-ethyl-S-a-chloromethyl-phosphonic acid ester are added withstirring at 50 C. The temperature is maintained at 80 C. for an hour;the reaction product is then diluted with 300 ml. of benzene and theseparated potassium chloride is filtered off. The benzene solution iswashed several times with water and subsequently dried with sodiumsulfate. By fractionation 30 grams of the new ester of B.P. 125 C./0.01mm. Hg are obtained. Yield 81% of the theoretical.

Aphids and spider mites are killed completely with 0.001% solutions.Larvae are killed to 100% with 0.00001% solutions. 0.01% solutions killblowflies to EXAMPLE 6 C2Hs S O OCzHr,

60 grams of 0.0--diethyl-thiolphosphoric acid ammonium salt aredissolved in ml. of methyl ethyl ketone. 66 grams ofethyl-thiono-O-ethyl-S-a-chloromethylphosphonic acid ester mol) areadded with stirring at 70 C. and heated for a further 2 hours to 7580 C.The

reaction product is then diluted with 200 ml. of benzene and washedtwice each time with 100ml. of water. After drying with sodium sulfatethe solvent is well removed in vacuum. In this way 40 grams of the newester as a weakly yellow water-insoluble oil are obtained. Yield: 37% ofthe theoretical. 27.3%; P, 17.6%. Found: S, 26.8%; P, 17.5%.

On rats per es the new ester shows a toxicity of 5 rug/kg. LD 0.001%solutions kill spider mites to 100%. Aphids are killed completely with0.01% solutions. Ticks are killed to 100% with 0.005% solutions.

If instead of the ammonium salt of 0.0-diethyl-thiolphosphoric acidthere are used the corresponding equimolecular amounts of the ammoniumsalt of 0.0-diethyldithiophosphoric acid or of O-ethyl-thiolphosphoricacid dimethyl amide or of O-ethyl-phenyl-thiolphosphoric acid or ofdimethyl-dithiophosphinic acid there are obtained the followingcompounds:

EXAMPLE 7 N at 52 grams of Z-mercapto-benzothiazole are dissolvedin 200ml. of anhydrous alcohol. A sodium methylate solution is added to thesolution containing V mol of dissolved sodium. 66 grams 0 mol) ofethyl-thiono-O- ethyl-S-ot-chloromethylphosphinic acid ester are thenadded at 60 C. followed by heating to 60-70 C. for 5 hours. The reactionproduct is taken up in 300 ml. of benzene and washed several times withwater. After the usual working up 85 grams of the new ester are obtainedas a viscous yellow water-insoluble oil. Yield: 81% of the theoretical.Calculated for mol 349: N, 4.0%; S, 36.7%; P, 8.9%. Found: N, 3.8%; S,36.6%; P, 8.4%.

On rats per os the new ester shows a toxicity of 50 mg./ kg. LD Aphidsare killed completely with 0.01% solutions and spider mites are killedto 100% with 0.001% solutions.

By the same way but using instead of the Z-mercaptobenzothiazole thecorresponding equimolecular amount of Z-mercapto-benzoxazole there isobtained the following compound:

CzHsO 32 grams of dimethylamino-thiocarbamic acid sodium salt aredissolved in 200 ml. acetonitrile. 42 grams mol) ofmethyl-thiono-O-ethyl-S-a-chloromethyl phos- Calculated for mol 352: S,

6 phonic acid ester (B.P. 50 C./ 0.01 mm. Hg) are added at 60 C. withstirring. Stirring is continued at 65 C. for an hour and the reactionproduct placed in 500 ml.- of water. The separated oil is taken up inbenzene, separated from the water and dried with sodium sulfate. Afterdistillation of the solvent 42 grams of the new ester are obtained as aviscous yellow water-insoluble oil. Yield: 72% of the theoretical.

Spider mites are killed completely with 0.001% solutions. Aphids arekilled completely with 0.01% solutions.

EXAMPLE 9 C H: S

i" S-C Hz-SC N 20 grams of ammonium thiocyanate are dissolved in 150 ml.of acetonitrile. 42 grams mol) of methylthiono-O-ethyl-S-a-chloromethylphosphonic acid ester are added at 60 C. with stirring. Heating iscontinued at 75 C. for an hour and the reaction product taken up in 300ml. of benzene. The solution is washed with water. After separating anddrying the benzene solution is fractionated. 22 grams of the new esterof 3.1. C./0.01 mm. Hg are obtained. Yield: 48% of the theoretical. Theester is a colorless water-insoluble oil.

Flies and spider mites are killed completely with 0.01 solutions.

EXAMPLE 10 CzHaO OC2H5 40 grams of diethyl-thiolphosphoric acid ammoniumsalt are dissolved in 76 ml. of methyl ethyl ketone. 42 grams ofmethyl-thiono O-ethyl S-tx-chloromethylphosphonic acid ester mol) areadded at 60 C. with stirring. Heating is continued at 60 C. for 3 hoursand the reaction product taken up in 300 ml. benzene. The benzenesolution is washed three times, each time with 50 ml. of water. Thebenzene solution is separated from the water, dried and fractionated. 26grams of the new ester are obtained as a colorless water-insoluble oilwith El. C./0.01 mm. Hg. Yield: 39% of the theoretical.

Aphids and spider mites are killed completely with 0.001% solutions.

EXAMPLE 11 19 grams i mol) of methyl-phosphonic acid-O-ethyl-S-(a-chlorornethyl) ester of the following constitution:

O SCHz-Cl OOzHs are added dropwise with stirring at 60 C. to 16 grams ofdimethyl dithiocarbamic acid sodium salt dissolved in 100 mll. ofacetonitrile. Heating is continued for 2 hours to 70 C. and the reactionproduct is then cooled. The reaction product is added to 500 ml. ofice-water. The separated oil is taken up in 250 m1. benzene. Afterdistilling 01f the :benzene, 14 grams of the new ester remain as a crudeproduct. Yield: 51% of the theoretical.

The ester may be recrystallized from ethyl alcohol. White needles: M.P.142 C.

32 grams mol) of dimethyl-dithiocarbamic acid sodium salt are dissolvedin 150 ml. of acetonitrile. 42 grams (7 mol) of ethylphosphonicacid-O-ethyl-S-achloromethyl ester (B.P. 63 C./0.01 mm. Hg)are added with stirring. Heating is continued to 70 C. for 2 hours andthen working up as described in Example 11. 48 grams of the new esterare obtained as a yellow waterinsoluble oil. Yield: 84% of thetheoretical Calculated for mol 287: S, 33.4%; P, 10.8%; N, 4.8%. Found:S, 32.7%; P, 10.8%; N, 4.5%.

Spider mites are killed completely with 0.001% solutions and aphids arekilled to 100% with 0.01% solutions.

EXAMPLE 13 OH: CH

49 grams of the potassium salt of methyl-thiono-thiolphosphonicacid-O-ethyl ester (0.25 mol) are dissolved in 150 ml. of acetonitrile,whereupon while stirring there are added at 80 C. 22 grams of methylenebromide. The mixture is kept for 1 hour at 80 C. and then cooled at roomtemperature. 300 ml. of benzene are added and the reaction mixture ispoured into 200 ml. of icewater. The organic layer is washed neutral anddried over sodium sulfate. After distilling off the solvent there areobtained 24 grams of the above shown compound in the form of a slightlyyellowish water-insoluble oil. The yield amounts to 59% of thetheoretical.

Calculated for mol 324: S, 39.4%; P, 19.1%. Found: S, 39.3%; P, 18.96%.

On rats per os the new ester shows a toxicity of 10 mg./kg. LD Aphidsand spider mites are killed completely with 0.0001% solutions. Thecompound shows a systemic action against sucking insects and an actionagainst eating insects such as caterpillars.

38 grams of the potassium salt of ethyl-thiono-thiolphosphonicacid-O-ethyl ester are dissolved in 150 m1. of acetonitrile whereupon at80 C. there are added while stirring 35 grams of methylene bromide. Thetemperature is kept for 1 further hour at 80 C. and the mixture isworked up as described in the foregoing example. 59 grams of the aboveshown ester are obtained in the form of a yellowish water-unsoluble oil.The yield amounts to 84% of the theoretical. v

Calculated for mol 352: S, 36.4%; P, 17.6%. Found: S, 36.1%; P, 17.3%.

On rats per os the new ester shows a toxicity of 5 mg./kg. LD Aphids arekilled completely with 0.001% solutions. 0.0001 solutions kill spidermites completely.

EXAMPLE 15 88 grams mol) of cyclohexyl-thiono-thiol-phos- O CzHu .phonicacid-O-ethyl ester are dissolved in 150 ml. of

O C 2H 108 grams (0.5 mol) of the potassium salt ofisobutenyl-thionophosphonic acid-O-ethyl ester are dissolved in 200 ml.of acetonitrile whereupon there are added at C. 44 grams of methylenebromide. The reaction mixture is kept for 1 further hour at about 80 C.whereupon the working procedure is carried out as described in theforegoing examples. There are obtained 80 grams of the new ester of theabove shown formula as a slightly yellowish colored water-insoluble oil.The yield is 97% of the theoretical. On rats per os the new ester showsa toxicity of 500 mg./kg. LD

Calculated for mol 404: S, 31.7%; P, 15.4%. S, 31.7%; P, 15.3%.

Spider mites and aphids are killed completely with 0.1% solutions.

Fou nd:

EXAMPLE 17 CzHaO S S 73 grams (A mol) of the potassium salt of4-chlorophenyl-thionophosphonic acid-O-ethyl ester are dissolved in ml.of acetonitrile. While stirring there are added at 80 C. 22 grams ofmethylene bromide. While stirring and further heating is continued for 1hour (at 80 C.) the reaction is completed and the mixture worked up asdescribed in the foregoing examples; 68% of the theoretical of the aboveshown ester, i.e. 44 grams are obtained as a yellowish coloredwater-insoluble oil.

Calculated for mol 517: C1, 13.7%; S, 24.8%; P, 12.0%. Found: Cl, 13.7%;S, 24.8%; P, 12.1%.

On rats per os the new ester does not show any symptoms even with 1000mg./kg.

What is claimed is:

1. A compound of the formula wherein Y is a member selected from thegroup consisting of oxygen and sulfur; R is a member selected from thegroup consisting of lower alkyl, cyclohexyl, lower alkenyl, phenyl andchlorophenyl; R is straight chain lower alkyl and R is a member selectedfrom the group consisting of benzthiazole-(Z), bcnzoxazole-(Z), phenylCarbonyl, lower alkyl carbonyl in which the lower alkyl has up to 4carbon atoms, lower dialkyl wherein R stands for lower alkyl and inwhich X is a member selected from the group consisting of oxygen andsulfur and R and R are members selected from the group consisting oflower alkyl having up to four carbon atoms, straight chain lower alkoxyhaving up to four carbon atoms, phenyl, chlorophenyl, lower dialkylamido having up to four carbon atoms in each alkyl group and cyclohexyl.

2. The compound according to claim 1 wherein Y stands for sulfur, R andR stand for lower alkyl and R stands for lower dialkyl thioamido.

3. The compound according to claim 1 wherein Y stands for sulfur, R andR stand for lower alkyl and R stands for wherein R is lower alkyl.

4. The compound according to claim 1 wherein Y stands for oxygen, R andR stand for lower alkyl and R stands for lower dialkyl thioamido.

5. The compound according to claim 1 wherein Y stands for sulfur, R andR stand for lower alkyl and R stands for wherein X stands for sulfur, Rstands for lower alkyl and R stands for lower alkoxy.

6. The compound of the following formula CrHs S 7. The compound of thefollowing formula C2115 S S 8. The compound of the following formula C HI? ll 021150 9. The compound of the following formula 02115 i ll PsoHzs-oN(oH,

CzHs

It]. The compound of the following formula CzH O S S OCzHs PSCH2SP C H3C H;

References Cited by the Examiner UNITED STATES PATENTS 2,429,178 10/1947Anish 260-3074 2,450,777 10/1948 Allen et al. 260306 2,862,019 11/1958Schrader 260-461 2,873,228 2/1959 Willard et al 260461 X 2,881,2014/1959 Schrader 260461 2,885,430 5/1959 Scherer et a1 260-461 2,907,78710/1959 Hoffman et a1, 260-461 2,908,605 10/1959 Beriger et al 260461 X3,008,977 11/1961 Schrader 260-461 FOREIGN PATENTS 1,025,200 2/ 1958Germany.

OTHER REFERENCES Kabachnik et al.: Zhur. Oschei Khirn, vol. 28, pp.1568-1573 (1958).

CHARLES B. PARKER, Primary Examiner.

IRVING MARCUS, MORRIS O. WOLK, JOSEPH P.

BRUST, Examiners.

1. A COMPOUND OF THE FORMULA